OBJECTIVE To examine the interaction between the GABA and glutamate neuronal systems. In the first experiment, we measured developmental changes in release of LHRH, GABA, and glutamate in the S-ME. LHRH levels were very low in prepubertal monkeys, increased to higher levels in early pubertal monkeys, with the highest LHRH levels occurring in midpubertal monkeys. As we previously observed, GABA levels were high in prepubertal monkeys and then decreased in early and mid- pubertal monkeys. In contrast, glutamate levels were very low in prepubertal monkeys, increased dramatically in early pubertal monkeys, and then slightly decreased in midpubertal monkeys, although midpubertal levels remained much higher than prepubertal levels. In the second experiment, we measured GABA, glutamate and LHRH in the same samples obtained from prepubertal monkeys which were infused with an antisense oligodeoxynucleotide (AS) for glutamic acid decarboxylase (GAD) 67 mRNA into the S-ME. GAD67 is a catalytic enzyme for GABA synthesis from glutamate, and AS GAD67 mRNA interferes with GAD67 synthe sis. Infusion of the AS GAD67 induced a decrease in GABA release, which subsequently resulted in an increase in LHRH release. Surprisingly, glutamate release also increased several hours after the decrease in GABA release, and the increased LHRH release continued. These data are interpreted to mean that a decrease in GABA synthesis by interference with GAD67 synthesis and the reduction of GABA release in the S-ME trigger an increase in LHRH release, but that a subsequent increase in glutamate release in the S-ME further contributes to the pubertal increase in LHRH release at the onset of puberty. The data further support our hypothesis that GAD plays an important role in the mechanism of the onset of puberty. FUTURE DIRECTIONS We will examine the causal relationship between GABA reduction and glutamate increase. KEY WORDS GABA, glutamate, GAD, antisense DNA, puberty FUNDING NIH HD11355 & RR00167 PUBLICATIONS Terasawa, E., Luchansky, L.L., Kasuya, E. An increase in glutamate release follows a decrease in((-aminobutyric acid (GABA) and the pubertal increase in LHRH release in female rhesus monkeys. Abstracts for the 80th Annual Meeting of the Endocrine Society, held June 24-27, 1998, at New Orleans, LA. p. 58 (OR5-2). [A]